CIHM 
Microfiche 
Series 
(IMonographs) 


ICIMH 

Collection  de 
microfiches 
(monographies) 


Canadian  Instituta  for  Historical  IMlcroraproductions  /  institut  Canadian  da  microraproductions  hittoriquaa 


Tachnical  and  BiMioflraphic  NotM  /  NoMt  tachniqiMS  at  biMioflrapliiqua* 


Tha  Inttitula  hat  anamptad  to  obtain  tha  batt  orifinal 
copy  availabia  for  filming.  Faaturat  of  this  copy  wliich 
may  ha  MMiofrapbicaliy  imiqiM,  which  may  altar  any 
of  tha  imagH  in  tha  raproduction,  or  which  may 
tignif icantiy  dianga  tha  usual  mathod  of  filmint.  ara 
chackad  balow. 


L'Institut  a  microfilm*  la  maillaur  axamplaira  qu'il 
lui  a  M  possiMa  da  sa  procurar.  Las  cMails  da  cat 
amamplaira  qui  sont  paut-Atra  uni<|uas  du  point  da  vua 
bibtiofraphiqua.  qui  pauvant  modif  iar  una  inwfa 
raproduita.  ou  qui  pauvant  axifar  una  modification 
dans  la  mMioda  normala  da  f ibnafa  sont  indiqufa 
ci-dassous. 


0Colourad  covars/ 
Couvartura  da  coulaur 

0Co«ars  damagad/ 
Couvartura  andommagia 

□  Covars  rastorad  and/or  laminatad/ 
Couvartura  rastaurto  at/ou  palliculte 

□  Covar  titia  missing/ 
La  titra  da  couvartura  manqua 


D 

D 


Colourad  r;aps/ 

Cartas  gtographiquas  an  coulaur 

Colourad  ink  (i.a.  othar  than  Mua  or  Mack)/ 
Encra  da  coulaur  (i.a.  autra  qua  Maua  ou  noira) 


□  Colourad  platas  and/or  illustrations/ 
Planchas  at/ou  illustrations  an  coulaur 


n 


Bound  with  othar  matarial/ 
Ralii  avac  d'autras  documants 

Tight  binding  may  causa  shadows  or  distortion 
along  intarior  margin/ 

La  raliura  sarria  paut  causar  da  I'ombra  ou  da  la 
distorsion  la  long  da  la  marga  intiriaura 

Blank  laavas  addad  during  rastoration  may  appear 
within  tha  taxt.  Whanavar  possiMa.  thasa  hava 
baan  omittad  from  filming/ 
II  la  paut  qua  caruinas  pagss  blanchas  ajouttes 
lors  d'una  rastauration  apparaissant  dans  la  taxta, 
mais,  lorsqua  cala  *tait  possiMa.  cas  pagas  n'ont 
pas  M  f  ilmias. 


□  Colourad  pages/ 
Pagas  da  coulaur 


0 


PagM  damaged/ 
Pagas  andommagees 


□  Peges  restored  end/or  leminated/ 
Pages  resteurias  at/ou  paNieuMes 


0 


Pages  discoloured,  ttakiad  or  foxed/ 
Pages  dicolorias,  techeties  ou  piqutes 


□  Pages  deteched/ 
Peges  dMaehtos 

0Showthrough/ 
Trensperence 


D 


Quelity  of  print  varies/ 
Qualite  inigele  de  I'impression 


□  Continuous  peginetion/ 
Pegination  continue 


D 


Includes  indexies)/ 
Comprend  un  (dest  index 

Title  on  haeder  taken  from:/ 
Le  titre  da  I'an-tlte  provient: 


n 


Title  pege  of  issue/ 

Page  de  titre  dc  la  livraison 


I       I  Caption  of  issue/ 


D 


Titre  de  dipert  de  la  livraison 

Mastheed/ 

Ginirique  (piriodiques)  de  la  livraison 


0 


Additional  comments:/ 

Commantaires  suppltmentairas:   Copy  has  manuscript  annotations. 


There  are  some  creases  in  the  middle  of  the  pages. 


This  ittm  is  filmed  at  tha  reduction  ratio  checked  below/ 

Ca  document  est  f  ilmi  eu  teux  de  reduction  indiqui  ci-dessous. 


10X 

14X 

18X 

22X 

26X 

30X 

y 

12X 


1CX 


aox 


24X 


2IX 


32X 


The  copy  filmtd  h«r«  has  b««n  rapreduesd  thanks 
to  th«  ganarotitv  of: 


Arekivw  of  Ontario 
Toronto 


L'Momplairo  filmi  fut  raproduit  grica  i  la 
g«n4rosit*  da: 

ArehlvM  puMlqiiM  dt  I'Ontvio 
TofOfito 


Tha  imagaa  appaaring  hara  ara  tha  bast  quality 
possibia  considaring  tha  condition  and  iagibility 
of  tha  original  copy  and  in  liaaping  with  tha 
filming  contract  apacif icationa. 


Las  imagas  suivantas  ont  At*  raproduitas  avac  la 
plus  grand  soin,  eompta  tanu  da  la  condition  at 
da  la  nattat*  da  I'aiiamplaira  film*,  at  an 
conformM  avac  laa  conditiona  du  contrat  da 
filmaga. 


Original  eoptas  in  printed  paper  eovars  ara  fUmod 
beginning  with  tha  front  cover  and  ending  on 
the  last  page  with  a  printed  or  illustrated  impraa- 
sion,  or  the  bacic  cover  when  appropriate.  All 
other  original  copiea  are  filmed  beginning  on  the 
first  page  with  a  printed  or  illustrated  imprae- 
sion,  and  ending  on  the  last  page  with  a  printed 
or  illuatratad  impreaaion. 


Lee  esemplaires  originaux  dont  la  couverture  tn 
papier  est  imprim«e  sent  film4s  en  eommencant 
per  le  premier  plat  at  en  terminant  soit  par  la 
damlAre  page  qui  comporte  une  empreinto 
d'Imprassion  ou  d'illustrstion,  soit  par  le  second 
plat,  selon  le  cas.  Tous  Iss  autres  oxemplairas 
originaux  sent  filmds  •n  eommencant  par  la 
premiere  page  qui  comporte  une  empreinte 
d'impression  ou  d'illustrstion  et  en  terminant  par 
la  dami*re  page  qui  comporte  une  telle 
empreinte. 


The  last  recorded  frame  on  eech  microfiche 
shsll  contain  the  symbol  ^-^  (meaning  "CON* 
TtNUEO").  or  the  symbol  Y  (meaning  "END"), 
whichever  appliaa. 


Un  dee  symbolas  suivants  spparaltra  sur  la 
darniAre  image  do  cheque  microfiche,  selon  le 
cas:  la  symbols  -»>  signifis  "A  8UIVRE".  le 
symbols  ▼  signifis  "FIN". 


Maps,  plates,  charts,  etc..  may  be  filmed  at 
different  reduction  ratios.  Thoss  too  large  to  be 
entirely  included  in  one  exposure  ere  filmed 
beginning  in  the  upper  left  hsnd  comer,  left  to 
right  end  top  to  bonom,  ss  msny  frames  ss 
required.  The  following  diagrams  illustrsts  the 
method: 


Les  csrtss.  planches,  tableaux,  etc.,  peuvent  *tre 
filmte  A  dss  taux  da  reduction  diffSronts. 
Lorsque  le  document  est  trop  grsnd  pour  4trs 
rsproduit  sn  un  seul  clich*.  il  est  filmi  i  psrtir 
de  I'sngia  supArieur  gsuche.  de  gauche  *  droite. 
et  de  haut  en  bas,  mn  prenant  le  nombre 
d'imeges  ndcessaire.  Les  diagrsmmss  suivsnts 
illustrent  la  mdthode. 


1  2  3 


1 

2 

3 

4 

5 

6 

Ancient  Factors  in  the  Relations  between 
the  Blood  Plasma  and  the  Kidneys 


BY 

A.  B.  MACALLUM,  M.D.,  F.R.S. 
noTMMM  or  Koomunnvr  w  nn  VNimMrrr  «m  kmomto 


PUM  THE 

AMERICAN  JOURNAL  OF  THE  MEDICAL  SCIENCES 
July,  1918,  No.  1,  \-oi.  dvi,  p.  1 


Estnrtcd  from  the  AmnieMi  Journal  of  th*  Medical  Beteneee, 
July,  1«18.  No.  1,  vol.  elv4,  p.  t 


AHcmn  VACTOBS  nr  the  ULAnom  bbtwihi 

BLOOD  FLABMA  AMD  TBI  KDlfin.' 


Bt  a.  B.  Macallum,  M.D.,  F.R,S., 

niorEaaoB  or  ■looiBiiianiT  m  nn  umvaMrrr  of  Toaoirro. 


The  -'^nism,  excq>t  that  of  the  unicellular  type,  is  a 

congerii  -    whose  history,  individually  considered,  as  it  is 

thus  i.  i,  constitutes  the  sciences  we  call  onnparative 

embry)  .jmpar»tive  physiology  and  which  we  must  know, 

not  only  . .  oipreht .  '  the  full  significance  of  the  work  they  now 
perform,  but  aba  to  leoognize  and  interpret  the  possible  variants 
from  the  norma'  in  function  and  structure  which  they  may  manifest. 
This  history,  in  invertebrates  as  in  vertebrates,  is  one  of  change 
either  in  structure,  or  in  function,  or,  often,  in  both  structure  and 
function,  and,  accordingly,  frequently  confusing  and  difficult  to 
follow  m  any  attonpt  to  gain  a  full  comprehenaon  of  the  conditions 
and  forces  tiiat  determined  the  diaracter  of  etidi  organ. 

One  needs  but  to  scan  the  list  of  the  organs  of  the  vertebrate 
body  to  illustrate  how  true  this  is.  The  nervous  system  with  its 
protean  numifestations  in  the  line  of  evolution,  the  thyroid,  the 
thymus,  the  suprarenals,  the  pituitary  body,  the  pineal  gland,  the 
gills,  the  lungs,  the  alimentary  canal  with  its  accessiny  structives 
and  even  the  liver,  all  have  a  past  in  which  the  dominant  feature  has 
been  changed  in  structure  and  fimction  with  the  result  that  the 
final  stage  in  each  transcends  the  eariier  ones  and  so  obscures  their 
characters  that  it  is-  now  difficult  to  determine  the  earlier  history 
except  in  some  cases  from  the  structural  side. 

One  thing  is  mdeed  certain.  The' change  has  never  been  of  the 
■per  aaUum  type.  But  it  has  been  unceasing,  without  pause,  and  it 
b  progressmg  today  as  it  has  been  in  the  long  past.  The  Hera- 
deitan  flux  therefore  plays  its  part  in  organogenic  evolution  as 
distinctly  as  it  does  in  the  physiod  world. 

Among  all  the  organ?  with  their  varied  history  as  to  structure 
and  their  variations  L.  fxmction,  there  is,  however,  one  whose 
function  in  one  particular  respect  has  not  changed  from  the  time 

■  The  Hatfield  Lecture  delivered  l>afora  the  CoUcfe  of  Phjrsiriau,  PhOadelpbia, 
April  10,  1017. 


2         iiACALum:  TBI  BLO<»  nuMJL  Am  TBI  xmNxn 

when  it  first  began  to  evdve  in  the  very  far  past  Thia  wgan  is 
the  kidney  and  the  function  ^;hid)  it  performs,  as  it  has  performed 
it  far  back  in  the  very  beginning  of  the  history  of  vert<^te  life, 
is  the  regulation  of  the  inwganic  composition  of  the  internal 
medium  (rf  the  body,  whidi  we  know  as  tlw  Mood  idasma. 

Hus  organ  was  am<Hig  the  very  first  to  appear  in  the  prutoverte- 
brate,  or  in  the  first  invertebrate  type  whidi  hegta  to  (Merentiate 
along  the  line  of  devdoixnent  whidi  resulted  in  the  aiq>earanoe 
of  th^.  protovertebrate  in  the  Cambrian,  at  it  may  be  pre^^ambrian 
times.  If  vre  may  rdy  on  the  order  in  whidh  the  organs  appear 
in  the  euibryologiad  history  of  the  vertebrate,  the  renal  organ  is  as 
ancient  as  the  neural  canal,  a.nd  its  otypn  would  appear  to  antedate 
by  a  long  period  the  dosure  of  this  canal  and  the  disappearance  of 
the  coelomic  cavity  into  which  the  primitive  nephric  tubules  opened. 
If  the  latter  are,  as  has  been  claimed,  derived  by  differentiation  fr(»n 
the  coxal  ^ands  of  a  crustaoean<4ike  form,  they  are  of  more  andent 
origin  than  the  neural  canal  itsdf . 

What  the  kidney  of  the  protovertdnate  was  we  may  gather  firom 
the  eariiest  imm  of  the  vertebrate  kidney,  which  consisted  of 
three  divisions,  arranged  in  order  frmn  before  badcward:  the  pro- 
nephros, the  mesonephros  and  the  metanqdiros.  One  of  tb<se,  the 
mesonephros,  becomes  the  adult  kidney  in  fishes  and  ^phibia; 
ano^er,  the  metanephros,  becomes  the  functional  kidney  m  other 
vertebrate  classes,  reptiles,  birds  and  mammals.  This  is  of  sig- 
nificance, as  I  shall  show  later,  in  indicating  that  the  regulation  of 
the  inorganic  composition  of  the  blood  plasma  exercised  by  the 
adult  kidney  must  have  been  exercised  also  by  the  kidney  of  the 
protovertebrate. 

In  order  to  understand  what  thb  regulation  involves  we  must 
for  a  moment  consider  what  the  inorganic  OMnposition  of  the  bk)od 
plasma  is.  The  salts  of  the  blood  plasnw  in  amount  range  between 
0.78  and  0.88  per  cent,  of  the  weight  of  the  plasma,  and  they  consist 
of  the  chlorides,  phosphates,  carbonates  and  sulphp'^es  of  sodium, 
potassium,  caldum  and  magnesium.  The  salts  of  sodium  are  by 
far  the  most  abundant,  after  which  come  those  of  potassium,  cal- 
cium and  magnesium  in  the  order  mentioned.  Tk  j  salts  of  sodium, 
chiefly  the  chloride,  amount  to  more  than  90  per  cent,  of  the  total 
inorganic  solids  of  the  plasma. 

The  composition  in  detail  has  been  determined  by  Bunge  for  the 
horse,  ox  and  pig,  and  by  Abderhalden  for  the  ox,  horse,  pig,  sheep, 
dog,  cat. 

lie  composition  of  human  plasma  has  not  been  redetermined 
since  1850  when  Carl  Schmidt  published  the  results  of  a  number  of 
analyses  which  are  quoted  now  m  all  the  text-books.  They  were 
obtained  by  the  methods  in  use  seventy  to  eighty  years  ago,  which 
gave  less  exact  determinations  than  those  now  followed  in  making 
such  analyses,  and,  consequently,  the  percentages,  notably  those 


macallvm:  tbb  blood  plasma  and  thb  eonibtc 

of  potMunn,  cmldum,  magnetium  and  dilorine,  whidi  Sdunidt'i 
deteraunatioBS  yield,  ue  open  to  quettion. 

Hie  inorganic  oompoMtion  of  the  plaana  in  binU,  reptiles  and 
amphibia  has  not  been  ascertained,  but  the  total  peroentacs  of  tho 
ash  has  been  ascertained  to  range  between  0^  and  0.9  in  birds  and 
reptiles,  while  b  the  frog  it  has  been  estimated  to  be  as  km  as  0.46, 
but  this  may  possibly  be  due  to  the  diflkuHy  of  getting  enou^  of 
the  idasma  of  the  frog  fr«e  from  admoture  with  water  or  lymph. 
The  fact  that  in  birds  and  reptiles  the  percentage  ct  the  salts  is 
as  hi^  as  in  mammals  is  an  indicatitm  that  the  details  of  the 
composition  are  not  widdy  different  from  those  of  the  plasma 
of  the  nuunmsis  abovo  mentioned. 

The  analyses  of  ttie  bloc !  plasma  m  fishes  whidi  we  have  today 
are  only  those  of  thu  cod,  ptjlock  and  dogfish,  which  I  made  dght 
years  ago,  and  they  are  of  q)ecial  interest  in  connection  with  the 
aniJyses  (rf  the  Mood  pUsma  of  mammals. 

If  one  examine*-  Bunge's  and  Abderiialden's  tables,  giving  the 
results  <k  their  analyses,  one  is  impressed  only  with  the  fact  that  the 
detsils  obtrude  themselves  to  the  exdiision  of  all  else,  that  in  fact 
one  does  not  see  the  woods  for  the  trees,  and,  in  consequence,  the 
ngnificanoe  of  the  results  are  obscured. 

If,  however,  one  selects  the  catiimic  elements  and  arranges  them 
in  values  proportional  to  the  most  abundant  one,  sodium,  which 
may  be  made  equal  to  100,  order  is  obtained  frran  the  mase  of 
details  in  these  uudyses,  a^d  one  finds  surprising  reaemUanoes  in 
the  ■wdues  obtained  frwn  plasmas  (rf  all  the  mammals.  FurthCT,the 
proportions  obtained  frran  the  analyses  of  the  {dasLja  of  the  fishes 
referred  to  fall  bto  lice  witl  t  tne  fran  mammalt,  in  such  a  way  as 
to  suggest  that  we  have  thus  revealed  a  cardinal  feature  in  the 
inorganic  compositiob  of  the  blood  pbuma  ci  \-^tebrates. 

TUs  feature  is  indicated  in  the  fdkr.  ing  table  of  ratios  in  which 
Na  -  100. 


Nk. 

K. 

Ck. 

Ml. 

DucSdi  UeanOtiat  lulaaru) 

100 

4.01 

3.71 

3.40 

100 

0.600 

3.03 

1.47 

FoUoek  (PsBcmMiu  tireiu)  . 

100 

4.SS 

3.10 

IM> 

Do* 

100 

«.8S 

3. S3 

0.81 

MMDBUd  (•«•««•)    .       .       . 

lOO 

e.oo 

3.68 

o.ao 

Man  (C.  Schmidt)    .     .     . 

100 

9.23 

3.37 

1.7S 

Mu  (A.  B.  M-)  .     .     .     . 

100 

S.U 

8.71 

0.86 

The  ratios  for  man  are  -derived  from  Schmidt's  analyses  carried 
out,  as  already  stated,  with  methods  which  wer  ^  less  exact  than  those 
which  are  employed  today,  and,  in  consequence,  they  are  accepted 
with  reserve,  more  especially  as  in  my  own  determinations  on  the 
blood  plasma  of  man  the  values  for  potasaum,  calcium  and  mag- 
nesium are  much  lower  than  those  given  by  Schmidt  and  in  general 
accord  with  those  of  Abderhalden  and  Bunge  for  manmuls. 

Tlie  ratio  of  potassium  in  the  blooid  plasma  of  the  cou,  as  Jeter- 


macaixom:  thk  vumd  plasma  and  the  kidnsts 


mined  in  my  own  anaiyMB.  is  hif^,  but  this  may  fomAhky  be  due 
to  hemolysis,  the  prepantion  of  serum  which  I  used  having  •  red- 
dish tinge  and  therefore  probably  contained  the  potassium  ol  the 
hemolyud  oorpuacles,  which  thus  would  give  a  higher  ratio  for 
this  element  tlwn  would  be  given  by  pure  plasma  or  serum.  The 
fact  tint  so  near  a  relative  of  the  cod,  as  is  the  pollock,  gives  less 
than  half  ^  ratio  of  the  cod  and  approadies  vtry  closely  that  of 
the  do(^  supports  the  view  that  the  ratio  in  the  cod  is  less  than 
that  given  above. 

Apart  from  these  exceptions,  if  they  are  to  be  ranked  as  such 
and  not  due  to  errors  in  analysis  or  to  abnormal  composition,  the 
striking  feature  is  the  very  extraordinary  parallelism  between  the 
ratios  in  mammals  and  those  in  fishes.  Thb  parallelism  appears 
enhanced  when  one  consklers  that  the  concentrations  of  inorganic 
salts  in  both  classes  c^  vertebrates  differ.  The  concentrati-  i  in  the 
serum  of  the  mammal,  lis  already  stated,  ranges  from  0.78  to  0.88 
per  cent,  in  the  sera  of  the  cod  anti  pollock,  from  1.282  to  1.20:i, 
respectively,  while  in  the  dogfish  it  is  1.774,  or  {wactically,  double 
what  it  is  in  the  serum  of  a  mammal. 

The  parallelism  in  the  ratios  of  the  individual  elements  in  the 
highest  as  well  as  in  the  lowest  vertebrates  is  a  cardinal  fact,  some- 
thing more  fundamental  than  the  total  concentration  of  the  salts 
in  the  plasma.  Its  occurrence  in  two  such  widely  separated  classes 
of  vertebrates  suggests  that  it  is  an  endowir  -xt  received  from  the 
common  ancestor  of  both,  the  protrvertcbrate,  which  must  have 
existed  in  the  early  CamlHian  or  pre-Cambrian  times. 

What  is  the  explanation  of  these  ratios  between  the  sodium, 
potassium,  calcium,  and  magnesium? 

The  answer  tc  this  question  I  obtained  some  fourteen  years  ago 
when  determining  the  inorganic  composition  of  certain  medusae 
and  comparing  it  with  the  composition  of  the  ocean  water  of  their 
habitat.  Aurelia  flavidula,  the  common  jelly  fish  of  our  coasts  in 
July  and  August,  when  it  is  liquefied,  whidi  happens  when  it  is 
allowed  to  stand  in  a  dry  dish,  furnishes  a  liquid  in  which,  besides 
organic  constituents,  is  contained  a  concentration  of  inorganic  salts 
like  that  of  the  ocean  water  from  which  the  animal  was  taken. 
From  the  analyses  of  its  salts,  compared  with  those  of  ocean  water, 
ratios  between  the  sodium,  potassium,  calcium  and  magnesium 
(with  Na  -  100)  were  obtained  which  revealed  a  very  striking 
parailel. 

Ocean  water  (Dittmar)  . 
Aurelia  flavidula  (Macallum) 

The  parallelism  betw^een  the  two  series  of  ratios  is  very  close  and 
the  conclusion  follows  the'  :  fluid  in  the  tissues  of  Aurelia  is 
but  very  slightly  modified  t  .^-n  water  and  of  the  same  concentration 
as  the  latter. 


Na. 

K. 

Ck 

Mg 

100 

3.03 

3.01 

12.10 

100 

S.18 

4.13 

11.43 

MACALLVM:  the  BLUUD  FLMUU  and  tub  KlbNEYH  O 

It  WM,  however,  when  the  ntkw  for  w»  water  were  com|Nired 
with  the  ratios  c  f  the  blood  piMn»  of  •  .unnul,  for  enmi^.  the 
dog.  that  one  obtained  a  chie  to  iK  orif  .  of  the  rathm  in  the  blood 
pbunia  of  vertebrates.    We  we  in  tH'  ^tter: 


N*. 

K. 

Ol». 

Mfl 

OoMM  w«tMr  (DitUBu)     .     .     . 

100 
100 
100 
100 

I.ftl 

e.w 
i.ta 
a.TS 

a. 01 
a.sa 

4.00 
4.85 

13.10 
0.81 

n.ao 

1.73 

Jiat  the  ratios  are  parallel  to  thoee  of  ocean  water,  except  b  regard 
to  magneshim.  Were  the  ratio  of  the  hitter  reduced  to  1,  or  thnc- 
abouta,  the  paralleliam  between  the  two  awies  would  be  so  striking 
as  to  render  unneoesaary  further  diacuasion  of  th*  queation  of  th^ 
origin  of  the  ratio*  in  the  blood  i^aama. 

That  these  ratios  are  of  oceanic  wigin  can  admit  of  no  dou 
when  we  cmnpare  them  with  thoee  of  the  horseshoe  crab  ardlobntt.. 

The  horseshoe  crab.  Limulus  fdyphemua,  whidt  b<<s  kid  its 
habitat  in  the  ocean  aince  its  origin  in  the  early  por«.'>n  of  the 
Pabeozoic  age,  has  a  jJaama  in  vhidi  the  pa  -^  .  Jisni  betw  •:  v  \t  and 
ocean  water  is  uncontrovertible.  Thu  b  nc  '..bt  due  to  ;he  fact 
that  the  osmotic  preaui  .'  of  the  ocean  has  been  acting  on  its  plasma 
through  the  many  milUons  of  years  which  have  elapsed  since  the 
Cambrian  age,  and,  jdiough  unquesticmably  the  ocean  has  been 
undergoing,  in  all  that  time,  changes,  not  only  in  concentration  but 
also  in  the  ratios  of  its  salts,  the  Mood  plasma  of  the  horseshoe  crab 
has  kept  pace  wiUi  it  and  today  the  concentration  of  its  salts  equals 
that  of  tlue  ocean  water  in  whidi  it  lives,  and  the  ratios  in  its  pUuma 
are  practically  l^ose  of  ocean  water.  We  thus  see  that  ocean  water 
does  in  diis  one  case  determine  the  inorganic  composition  of  the 
blood  plasma. 

In  the  plasma  of  the  lobster,  Homarut  ammcanut,  whK'h  has  been 
associated  with  He  ocean  only  since  the  Cretaceous  pe  lod,  though 
the  concentration  of  the  inorganic  salts  b  as  hi^  as  the  ocean 
water  of  its  habitat,  the  ratio  of  the  magnesium  only  is  different 
from  that  of  the  ocean. 

In  both  the  lobster  and  the  horseshoe  crab  the  concentration  of 
the  inorganic  salts  of  the  plasma  appears  to  vary  with  the  concen- 
tration of  the  ocean  water  of  their  habitat,  and  in  brackish  water 
it  falls  to  that  of  the  latter.  The  concentration  of  the  salts  of  the 
plasma  in  these  forms  follows  the  concentration  of  the  medium, 
whereas  in  the  Seladiians,  which  include  the  shark:  and  \be  dogfish 
and  which  have  had  their  habitat  in  the  ocean  ever  smce  the  early 
part  of  the  Pabeozoic  age,  the  concentration  of  the  plasma  salts 
exceeds  half  that  of  ocean  water  to  a  slight  extent,  although  the 
osmotic  pressure  of  the  uoean  has  been  exerting  its  effect  on  the 
Selachian  plasma  for  at  least  several  scores  of  millbns  of  years. 


6  iiACALum:  ih>  blood  flabma  and  the  kidnitb 

In  the  marine  Teleosteui  fishes,  whidi,  like  the  ood,  have  been 
denizens  <rf  the  ocean  for  a  time,  periiaps,  not.  half  as  long,  the 
concentration  in  the  i^asma  is  but  little  more  than  a  third  of 
the  concentration  rf  the  salts  m  *iie  ocean. 

In  the  marine  invotebrates  of  today  the  circulatory  fluid  is  but 
a  more  or  less  modified  form  rf  sea  water.  In  some  the  circulatory 
channels  fiedy  communicate  with  the  exterior  with  the  result  that 
the  circulatory  fluid  is  pure  sea  water,  but,  even  wbea  the  circu- 
lation is  closed  as  it  is  in  the  horseshoe  crab,  the  blood  plasma  is 
sea  water  with  protons  and  other  organic  constituents. 

There  is  then  a  jwofound  difference  between  the  blood  plasma 
oi  vwtebrates  and  that  of  invertebrates.  That  of  the  latter  varies 
more  or  less  readily  with  an  immediate  change  in  the  medium  of 
the  habitat,  while  that  of  the  former  is  affected,  and  then  but 
appreciably,  only  after  milBons  <rf  years. 

Ate  we  then  to  condude  that  the  plasma  of  vertebrates  was 
primarily  of  wigin  different  from  that  of  the  plasma  of  inver- 

tebmtes?  ....  .     .  ,  . 

If  we  scan  the  tables  of  ratios  for  the  sodium,  potassium,  cakaum 
and  magnesium  in  the  i^asanas  6t  the  different  forms  of  vertebrates 
and  invertebrates,  we  see  m  the  paraUeliam  already  rderred  to  an 
unmistakable  indication  that  the  blood  plasma  of  vertebrates  was 
also  originally  sea  water,  not  indeed  the  aea  water  of  the  present 
age,  but  of  a  far  past  when  the  concentration  of  its  salts  was  less  than 
one-third  of  what  it  is  now  and  when  also  the  potassium  was  rela- 
tively more  a^  the  magnesium  rdativdy  less  abundant  than  m  the 

ocean  of  today.  ......  ,  .  .  -. 

The  sea  b  tiie  ori^nal  home  of  all  life  on  our  ^obe,  and  it  was 
m  the  sea  that  the  differentiation  between  amnua  and  vegetable 
life  as  well  as  the  evdution  of  tiie  great  divisbns  of  the  annual 
kingdom  were  effected.  Indeed,  the  great  events  in  the  evdu- 
tion  of  animal  forms  have  been  roidered  posnble  by  dianges  which 
have  taken  iJace  in  the  composition  of  the  ocean.  Among  the  fun- 
damental results  of  these  changes  was  the  devdoiMnent  of  a  closed 
circulatory  system  of  vertebrates,  the  fluid  contained  m  which 
became  henceforth  independent  of  the  ocmipoation  of  the  contempo- 
rary ocean,  and,  as  we  have  seen,  of  the  ocean  of  subsequent  periods 
even  after  many  millions  of  years,  as  in  the  case  of  the  Seladiians 
(sharks),  marine  Teleosts  (cod,  herring)  and  the  Cetaoea  (whales). 

The  sea  ever  since  the  first  condensation  of  water  on  the  ongmal 
cooled  rock  crust  of  our  ^obe  has  be«a  changing  in  composition  by 
the  leaching  out  of  its  bed  the  salts  it  contained  and  by  receiving 
salts  in  the  river  discharge,  also  leached  frwn  the  land  areas  of 
the  globe.  The  quantity  of  salts  annually  disdiarged  from  the 
land  areas  is  enormous  and  it  is  estimated  by  'Joly  at  about  one 
hundred  and  fifty-seven  nullions  of  tons  (157,270,000),  which,  if 
divided  into  the  amount  of  salts  which  he  calculates  as  contained  in 


I 


I 


macallum:  the  blcxh)  plasma  and  tbb  ramsTS  7 

the  ocesn  today,  mundy,  14,151,000,000,000,000  tons,  would  ^e 
the  age  of  the  ocean  as  aj^roximatdy  ninety  million  yean.  The 
concentration  has  theief(»e  been  slowly  dianpng  and  it  must  have 
been  in  the  far  past  much  less  than  it  is  now. 

The  idative  propcHlions  of  the  various  salts  must  have  duuged 
dso.  AH  the  salts  discharged  in  the  ocean  by  the  rivers  have  not 
been  retuned,  for,  woe  they  retained,  the  potassium  and  the 
calcium  salts  would  be  very  greatly  nuwe  abuiulant  than  they  are 
now.  Indeed  the  caldum  salts  in  the  ooean  would  have  long  ago 
reached  a  degree  (rf  high  supersaturation  quite  impossible  to  con- 
cave of,  since  the  Ume  saks  in  the  calcareous  rocks  of  the  earth's 
crust,  depodted  from  sea  water  in  the  past  ages,  woidd  thus  be  in 
sdution  in  the  sea.  The  potasdum  was,  <moe,  rdativdy  to  the 
sodium,  more  abundant  than  the  i»esent  ratio  indicates,  and  it 
has  been  and  is  being  constantly  -xtracted  fr«n  the  ocean  in  the 
formation  oi  such  minerals  as  glaiuionUe  apparentiy  at  a  rate  whidi 
keeps  its  concentration  over  long  ages  f airiy  constant.  The  mag- 
nedum  salts  also  have  bem  concentrating  slowly,  for  the  dinuna- 
tion  of  magnedum  as  cubonate  in  the  formation  of  ddomitic  lime- 
stone has  been  proceeding  at  a  rate  less  than  that  of  the  constant 
addition  throu^  the  river  water.  This  wouM  postulate  that  mag- 
nedum b  not  only  absdutdy  but  also  relatively  more  abundant 
in  the  ocean  of  today  than  it  was  in  that  of  the  far  past 

The  only  constituemts  that  are  not  extracted  from  the  ocean  are 
the  sodium  salts.  TTirae  have  always  therefcwe  been  on  the  increase 
from  a  time  in  the  eariy  pre-Cambiian  when  they  were  periiaps  but 
slightiy  in  excess  of  those  of  potasdum.  Their  increase  will  proceed 
in  the  ages  to  come  and  findly  produce  such  a  d^ree  of  concen- 
tration and,  consequentiy  sudi  a  speca&c  dendty  that  will,  as  in 
the  water  of  the  Dead  Sea,  pwmit  tiie  human  body  to  float  because 
d  its  lower  spedfic  gravity.  .... 

The  differences  in  the  series  of  ratios  exhibited  by  the  sodium, 
potasdum,  calcium  and  magnesium  in  the  blood  plaana  of  verte- 
brates on  the  one  hand  and  in  the  sea  wat»  of  today,  on  the  other, 
parallel  as  these  two  series  so  strikingly  are,  can  be  e^)lained  as 
due  to  the  blood  plasma  reproducing,  ai^roximately,  the  ratios 
obtaining  m  the  ocean  of  the  time  when  the  ori^nal  ancestral  form 
of  vertebrates,  the  i»otovortebrates,  ot  eovertd)rate8,  arose.  The 
total  concentration  of  the  salts  in  the  blood  plasma  can  also  be 
explained  as  due  to  a  reproducti<m  of  the  ooncratration  <rf  the  sea 
water  of  the  same  age,  that  is,  when  it  had  less  than  1  per  cent,  of 

salts. 

How  far  back  in  geolo^l  time  this  poiod  was  it  is  difficult  to 
detomine  exactiy.  It  must  have  been  eariier  than  the  earliest  w 
most  ancient  fosnl  ronains  of  vertebrates  indicate,  that  is,  in  the 
eariier  Cambrian  or  even  pre-C«nbrian,  for  the  |m>tovatdi>rate 
must  have  l<Mig  preceded  the  vtftdmtes  to  which,  throuf^  evdu- 


8 


hacallvm:  the  blood  plasma  and  the  kidnets 


tion,  it  gave  origin.  How  long  the  intervening  period  has  been  is 
also  difficult  of  detennination.  Estimates  made  on  various  bases 
give  different  results  and  the  only  satisfaction  that  one  obtains  from 
them  is  the  recognition  of  their  extreme  limits,  the  maximal  and 
minimal.  Prof.  Strutt  in  determining  the  content  in  helium  of  a 
nuneral  derived  from  Cambrian  rocks  of  Renfrew  Coimty,  Ontario, 
Canada,  calculates  that  it  was  over  seven  hundred  million  years  old. 
If,  on  the  other  hand,  one  follows  Joly's  method,  based  on  the 
amount  of  salts  in  annual  river  discharge  into  the  ocMn,  and  the 
amount  now  in  the  ocean,  and  also  acceptmg  as  approximatdy  co> 
rect  the  percentage  of  salts  in  the  ocean  when  the  protovertdbrate 
arose  as  less  than  1  per  cent.,  and  therefore  less  than  one-third  of 
the  concentration  in  the  ocean  of  today,  it  follows  that  more  than 
sixty  millions  of  years  must  have  elapsed  since  the  protovertebrate 
appeared  and  disappeared  on  the  geological  horizon. 

Whether  we  accept  the  higher  or  the  lower  estiouite,  or  even  a 
lower  one  still,  the  enormously  long  period  during  which  the  blood 
plasma  has  been  simulating  Palseo-oceanic  conditions  in  the  con- 
centration of  its  salts  and  in  the  ratios  of  the  sodium,  potassium, 
calciiun  and  magnesium  it  contains,  emphasizes  the  importance  in 
one  respect  of  ^e  organ  which  has  maintamed  through  the  long 
ages  of  vertebrate  history  this  concentration  and  these  ratios,  prac- 
tically unchanged. 

Thia  organ  is  the  kidney.  There  is  m  invertebrates  no  structure 
with  a  similar  function  or  with  a  function  even  distintiy  approaching 
that  of  the  vertebrate  kidney.  It  is  this  organ  that  has  made  a 
fundamental  difference  between  the  vertebrate  and  the  inverte- 
brate, not  only  in  the  struggle  for  existence  but  also  in  the  capacity 
to  evolve  higher  forms  of  animal  life.  The  animal  form  that  must 
accommodate  its  internal  medium  to  that  of  its  habitat  has  an 
enormous  handicap  when  it  changes  its  environment,  from  ocean 
to  fresh  water  or  to  land,  as  compared  with  one  whose  internal 
luediimi,  under  all  circumstances,  is  constant  in  composition.  With 
such  a  handicap  vertebrate  life  and  all  that  it  involves  would  have 
been  impossible. 

This  function  of  the  kidney  is  fundamental  and  is  more  ancient 
than  that  of  excreting  the  waste  products  of  the  tissues  of  the 
body.  In  the  dogfish,  as  in  Saladiians  generally,  whose  history 
has  been  associated  with  the  ocean  since  their  origin  in  the  Silurian 
period  and  in  whose  blood  plasma  the  concentration  of  salts  has  in 
consequence  been  incr«i^ed  to  only  about  half  that  of  the  sea,  the 
difference  between  tiie  osmotic  pressure  of  the  ocean  water  and 
that  given  by  the  salts  of  the  blood  plasma  is  equalized  by  urea 
which  amounts  to  more  than  2  per  cent^,  and  by  ammonium  salts, 
which  amounts  to  more  than  -^  reckoned  as  NH,.  This  retention 
of  urea  and  ammonium  salts  undoubtedly  developed  as  a  result  of 
the  tendency  of  the  blood  to  balance  the  slowly  increasing  osmotic 


IIACAIXUII:  THB  BLOOD  PLASMA  AND  THE  KIDNITB 


9 


pressure  of  the  sea  water.  The  very  fact  that  the  kidneys  in  these 
forms  exhibit  inertness  in  the  dinunation  of  urea  while  they  are 
extremely  active  in  the  diminatibn  of  salts  is  extremely  significant. 
What  th^r  do  most  rigorously  is  the  regulation  of  tiie  inorganic 
composition  of  the  blood,  theiefore  the  more  firmly  fixed  physio- 
logical habit  must  be  tiw  more  ancient  one  and,  consequently,  their 
earliest  function  was  not  the  elimmation  of  ^mtste  metabolic  products 
but  the  regulation  of  the  morganic  compoation  of  the  blood  plasma. 
The  function  of  excreting  waste  products  developed  later  and  in 
Selachians  never  acquired  the  fixity  that  diaracterizes  the  other 
function.  . 

In  the  long  ages  the  kidney  has  thus  performed  a  function  wtudi 
for  constancy  and  unvarying  regularity  is  unrivalled  in  the  world 
of  life.  This  constancy,  this  unvarying  regularity  contrasts  strik- 
ingly with  the  variation  in  function  which  the  other  organs  have 
undergone  and  indicates  how  basic  the  kidney  is  in  the  vertebrate 
system  and  why  it  takes  precedence  in  the  body  as  a  vertebrate 
organ  par  excellence. 

How  it  happened  that  the  kidney  in  the  protovertebrate  acquired 
this  fixity  of  function  we  do  not  know.  Geologists  concede  a 
very  long  time  to  the  pre-Cambrian,  a  duration  which,  according  to 
different  estimates,  ranged  from  one-third  to  nine-tenths  of  the  whole 
geological  period.  In  this  long  cycle  of  time  many  things  could 
have  happened  and  conditions  must  have  obtained  which  impressed 
on  the  primitive  kidney  of  tiie  protovertebrate  an  abiding  character, 
not  to  disappear  even  though  the  original  organ  underwent  a 
marked  transformation  in  structure  before  it  devel<q)ed  into  the 
renal  organ  of  the  vertebrate  of  today. 

The  question  now  arises,  whether  this  PaUeo-oceanic  character 
b  ever  disturbed  in  disease  of  the  kidney  and,  if  it  is,  what  are  the 

results.  ... 

To  this  question  there  is  not  much  to  offer  m  the  form  of  an 
answer.  There  have  been  very  few  investigations  of  the  morganic 
composition  of  the  blood  plasma  in  disease,  and  these  only  of  a 
very  limited  scope,  bearing  abnost  whdly  on  the  chlmine  content, 
t-e  amount  of  which  was  supposed  to  give  an  indication  of  the  total 
concentration  and  of  tiie  sodium  present.  The  conclusions  based 
on  such  analyses  are,  of  course,  accepted  only  with  reserve  amply . 
because  of  the  tenuity  of  the  data  on  which  they  are  based.  Plasma 
that  are  accessible  are  those  of  Schmidt. 

Believing  that  the  subject  had  possibilities  m  a  clinical  line,  I 
undertook  during  the  last  five  years  investigations  on  the  inorganic 
compoation  of  normal  human  plasma,  with  a  view  to  comparison 
of  the  same  with  the  blood  plasma  in  cases  of  Bright's  disease,  and, 
more  especially,  in  cases  Of  puerperal  eclampaa.  These  investiga- 
tions are  not  yet  completed,  owing  to  the  time-devouring  character 


10  ILXAIXUU:  THI  BLOOD  FLA81IA  AND  THB  KIDNKT8 

of  the  work  involved,  buc  ;KHne  of  the  results  so  far  obtained  are 
c^nite  and  interesting  »ud  they  may  be  mentioned  here. 

It  is  to  be  premised,  first  of  all,  that  the  determinations  m 
Sdmudt's  analyses,  so  far  as  sodimn,  potastdum,  cakaum  and  mag- 
nesimn  are  conconed,  give  too  high  values.  Those  for  sodium 
range  from  0.3173  to  0.3438  per  cent,  and  for  potassiiun  from  0.0314 
to  0.0332,  while  in  my  analyses  the  range  of  sodium  is  from  0.29  to 
0.316  and  <rf  potassium  frwn  0.019  to  0.0212.  It  may  thus  be  seen 
that  Sdmudt's  value»are  quite  too  hi^,  and  especially  in  the  case 
of  potasfflum,  his  average  fw  the  ktter  b«jng  60  p«  coit  in  excess 
of  mine.  The  results  obtained  for  the  plasma  in  Biij^t's  disease 
are  quite  incomi^ete,  but  those  for  puerperal  edampua  are  far 
enough  advanced  to  enable  me  to  give  some  points  of  interest. 

In  4  cases  the  ratios  on  the  bases  of  Na  -  100  were: 

Qmm  N».                    K.  C».  Mr 

1  ...  100  17. 68  4.02  3.42 

2  *'....  100  28.70  3.27  2.37 

3  '     '                 ....  100  10.(10 

4  ■     ■     ■           ....  100  10.10  2.58  0.68 
[SCnonniU)    !     ....  100                S.U  2.71  0.861 

The  magneaum  and  caldum  content  b  high  in  Cases  1  and  2 
and  normal  in  No.  4,  but  in  all  the  potassium  is  in  excess  and  m 
No.  2  extraordinarily  so,  as  much  as  four  tiries  the  normal,  while 
in  No.  1  it  is  nearly  three  times  the  normal. 

There  was  a  minute  quantity  of  hono^obin  in  the  serum  of  all 
the  four  cases,  as  revealed  by  the  spectroscope,  and  srane  of  the 
potassium  found  in  excess  of  the  normal  Jiay  have  beta  denved 
from  hemolyzed  red  corpusdes  which  are  rich  m  potasrium  salts, 
but  this  would  not  explam  the  excess  in  No.  2,  in  whidi  the  amount 
of  hemoglobin  in  the  swum  did  not  exceed  that  in  Nos.  3  and  4.  It 
b  possible  that  hemolysb  in  the  circulating  blood  may  be  responabl^ 
ultimately  for  thb  excess,  but  thb  does  not  explain  the  non-elinuna- 
tion  of  the  potassium  in  excess  above  normal  by  the  kWnj^. 
Temporarily,  at  least,  in  edampaa  the  cdlular  elements  of  the  kid- 
ney concerned  in  maintaimng  the  normal  ratio  of  potassium  in  the 
blood  plasma  must  suffer  a  partial  or  total  eclipse  of  function. 

I  am  inclined  to  infer  from  the  results  of  my  observations  that 
the  very  first  change  from  the  normal  to  the  definitely  established 
primary  condition  in  some  of  the  forms  of  Bright's  dbease  b  a  loss 
of  the  power  to  mabtam  the  Pateo-oceanic  ratios. 

The  structures  in  the  kidney  involved  in  maintaining  these  ratios 
are  the  proximal  convoluted  tubules,  which,  with  the  glomendi, 
are  derived  from  and  therefore  represent  the  oripnal  parts  of  Ae 
kidney  of  the  eariiest  vertebrates  and  of  the  protovcr*ebrates.  The 
proximal  convoluted  tubules  are  also  concerned  i^  reducing  the 
H-ion  concentration  of  the  blood,  for  they  secrete  add,  not  acid  salts, 
into  the  urine,  a  function  which  is  also  very  andent,  a  function  per^ 


macallum:  the  blood  vaaua  ajid  the  kidneys 


11 


f<«ined  in  mvertebrates  by  «U  the  ce'S  of  the  body  sitimted  near 
the  body  surface,  and  still  pcrfonned  intennittently  and  with  a 
hi^  decree  of  spedalization  by  the  gastric  i^ands  of  vert<  ates.  T-^ 
aome  invertebrates  other  tissues  have  spedaUzed  in  this  oi.itter  also, 
as  for  example,  in  the  sdivary  glands  of  the  carnivorous  moUuM 
DoHum  galea,  the  concentration  of  the  sulphuric  add  of  the  "  saliva  " 
of  wluch  exceeds  4  per  cent. 

It  may  be  that  the  function  of  preventing  the  ever-tending-to- 
mcrease  of  the  H-ion  concentration  of  the  blood  plasma  is  as  andent 
as  the  Palieo^)ceanic  function,  i  view  which  their  common  localiza- 
tion in  tbe  Droximal  tubules  supports. 

Enough  has  been  said  here  to  emphasize  the  view  that  behind 
the  functions  of  the  renal  organ  is  a  history  which  links  up  tiie 
human  body  with  the  far  past^th  an  age  of  the  earth  when  ite 
oceans  contained  caly  what  'wuld  now  be  regarded  as  brackish 
water  and  the  earliest  type  of  vertebrate  life  was  just  beginning  to 
appear  as  a  marine  form.  From  the  facts  advanced  it  will  be 
gathered  also  that  the  blood  jdasma,  so  far  as  its  inorganic  salts  are 
concerned,  is  but  a  reproduction  of  the  remotdy  andeut  ocean,  and 
that  it  is  an  heirloom  from  the  life  in 

"that  immortal  IM 
Whic*.  brousht  us  thiilMr," 

not  indeed  in  the  Words^  orthian  sense,  but  in  the  literal  one,  for 
the  sea  b  the  original  home  of  aU  life  on  the  ^obe  and  gave  our 
blood,  and,  accordiugly,  the  tissues  of  our  bodies,  a  character  that 
long  ages  have  not  ^aced  and  will  not  efface. 


'/ 


THE  AMERICAN  JOURNAL 

OF  THE  MEDICAL  SCIENdS 

Oaoaoa  Morbis  PnaaoL,  M.D.,  Editor. 
John  H.  Muhud,  Jb.,  M.D.,  Aanstant  Editor. 

Mcmthly.    Illuttnted.    1920  pagea  yearly.    Price,  tSJOO  per  aoiuim. 

rriHE  AMERICAN  JOURNAL  OF  THE  MEDICAL  SCIENCEel,  founded  in  18U,  Imi 
1  long  been  leeoKniaed  ••  the  leading  medieal  journal  of  the  EngUab-epeeking  taoe.  From 
the  Sttk  it  aought  the  epodMnaking  papera,  and  beooming  reoogniaed  aa  their  mHium, 
it  has,  in  turn,  been  am^^t  by  thoee  who  have  had  diacuveriee  or  real  advancea  in  the 
art  and  adenee  of  medicine  to  announce  in  ita  Department  of  Original  Artidea  During 
19U  Th0  Ameriean  Journal  will  atill  further  develop  a  f&ituie  that  haa  proved  moat 
uaeful  and  pc^mlar,  namely,  a  aeriea  of  Special  Artidiea,  written  by  prearrangement  with 
men  of  the  higheat  authMity,  and  covering  preaent-day  topiea  of  the  greatest  importance 
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PROGRESSIVE  MEDICINE 

A  QUAKTESLT  DiaiST  OF  iXXfUXCEB,  DBCOfBOn  AND  XMPBOVI- 

WBsn  nr  thb  bodical  amd  subgical  soiEircni.  covnnro  the. 

BVnBB  DOBIAIN  OF  MEDiCIlfK.  Edited  by  Hobabt  Auoby  Habb,  M.D., 
ProfesBor  of  Therapeutics,  Materia  Medica  and  Diagnoaia  in  Jefferson  Medical  CoUege, 
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